title: Synthesis and biological evaluation of thiophene-C-glucosides as sodium-dependent glucose cotransporter 2 inhibitors.
abstract: The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.
authors.affiliation: Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sakamaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawanishi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Koga
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kuriyama
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Ueta
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Nomura
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*
chemical_list: C588047:(1S)-1,5-anhydro-1-(5-chloro-4-(4-ethylbenzyl)-2-thienyl)-D-glucitol; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D013012:Sorbitol; D005947:Glucose